Recent work in this laboratory has shown that lead exposure during the first ten days of life can produce behavioral abnormalities in rats eight weeks later even though gross signs of lead toxicity are not seen. Biochemical and morphological defects are also produced by lead in these animals. The greatest impairment is associated with enzymes associated with elements involved in blood-brain barrier function. The relationship of the enzyme inhibition to factors such as lead dose, tissue lead levels and age at time of exposure remains to be established. The reversibility of these effects and the degree of impairment of blood-brain barrier function associated with the observed enzyme inhibition is also unknown. This proposal describes an approach which will be utilized to determine the effect of low level lead exposure on selected biochemical and functional parameters associated with blood-brain barrier development. Brain and blood lead levels will be determined to relate lead effects on each parameter to tissue lead levels. Neonatal rats will be given lead acetate (7.5 mg/kg, i.p.) and utilized for in vivo amino acid and EDTA brain uptake studies or in vitro determinations of brain gamma glutamyltranspeptidase and butyrylcholinesterase activities. Age comparison studies of lead susceptibility will be conducted to compare lead effects and tissue lead levels produced in two age groups which possess different lead sensitivites. The effect of lower lead doses on these parameters will be measured in different brain regions to estimate the lead dose and tissue levels at which no discernible effects are produced. The results of this investigation will answer essential questions concerning the relationship betwenn lead dose, blood and brain lead levels produced and their effects on biochemical and functional indices of blood brain barrier development. These results will facilitate the development of a relationship between enzyme and functional disturbances produced in these studies and lead toxicity in children.